Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor.
Treatment of cells with granulocyte colony-stimulating factor (G-CSF) leads to tyrosine phosphorylation of cellular proteins. G-CSF stimulates both the activation of protein tyrosine kinases Lyn, Jak1, and Jak2 and the association of these enzymes with the G-CSF receptor. Wild-type, lyn-deficient, and syk-deficient chicken B lymphocyte cell lines were transfected with the human G-CSF receptor, and stable transfectants were studied. G-CSF-dependent tyrosyl phosphorylation of Jak1 and Jak2 occurred in all three cell lines. Wild-type and syk-deficient transfectants responded to G-CSF in a dose-responsive fashion with increased thymidine incorporation, but none of the clones of lyn-deficient transfectants did. Ectopic expression of Lyn, but not that of c-Src, in the lyn-deficient cells restored their mitogenic responsiveness to G-CSF. Ectopic expression in wild-type cells of the kinase-inactive form of Lyn, but not of the kinase-inactive form of Jak2, inhibited thymidine incorporation in response to G-CSF. These studies show that the absence of Lyn results in the loss of mitogenic signaling in the G-CSF signaling pathway and that activation of Jak1 or Jak2 is not sufficient to cause mitogenesis.
Corey
S J
SJ
Division of Hematology-Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. corey@med.pitt.edu
Dombrosky-Ferlan
P M
PM
Zuo
S
S
Krohn
E
E
Donnenberg
A D
AD
Zorich
P
P
Romero
G
G
Takata
M
M
Kurosaki
T
T
D000818:Animals; D002460:Cell Line; D002645:Chickens; D004261:DNA Replication; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D019061:src-Family Kinases